It has been known for over a century that the small intestinal mucosa contains a substance(s) which decreases glucosuria in diabetic patients (1), with the term “incretin” (i.e., the assumption that intestinally derived substances are involved in regulation of postprandial insulin secretion) being first coined by La Barre (2) in 1932. Proof of the incretin concept came with the observation that orally administered glucose gave rise to a much larger insulin response than when the same amount of glucose was given intravenously (3,4). Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the major incretin hormones in humans (5,6). Together, they account for up to 70% of postprandial insulin secretion in healthy subjects (7). In individuals with type 2 diabetes, however, the incretin effect is severely impaired (8). It is now widely accepted that this is largely the result of reductions in the insulinotropic activity of both incretin hormones (9,10), although in some patients an impaired secretion of GLP-1 may also contribute (11). A classic method for establishing the role of a given peptide is to infuse it in such a way as to mimic normal physiological plasma concentrations. By giving GLP-1 and GIP by variable infusion rate to copy their normal postprandial plasma profiles, Vilsbøll et al. (12) demonstrated that both incretin hormones contribute almost equally to the incretin effect in healthy subjects. However, …